Triple Negative Breast CancerPhase 2NCT03193853

TAK-228 and TAK-117 Followed by Cisplatin and Nab Paclitaxel for Metastatic Triple Negative Breast Cancer

A Phase 2 study testing Tak-228 & Tak-117 and Cisplatin & Nab Paclitaxel in people with Triple Negative Breast Cancer, run by Joyce O'Shaughnessy at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study evaluates efficacy of TAK- 228 and TAK- 117 followed by cisplatin and nab paclitaxel in patients with metastatic triple negative breast cancer. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Triple Negative Breast Cancer
What is being tested?: Tak-228 & Tak-117 and Cisplatin & Nab Paclitaxel
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 18 Jul 2017to 1 Dec 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female patients 18 years or older.
Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required.
Have not received more than 3 prior chemotherapy regimens for metastatic disease. Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is permitted.
Androgen receptor-negative (less than 10% positive nuclei) on standard IHC performed at the local pathology laboratory.
Have locoregional (eg, breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (See Appendix I)

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Female patients who:
Are postmenopausal for at least 1 year before the screening visit, OR
Are surgically sterile, OR
If they are of childbearing potential, agree to practice 1 effective methods of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling [eg, USPI, SmPC, etc,]) after the last dose of study drug, OR
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
Screening clinical laboratory values as specified below:
Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 10^9; platelet count ≥ 100 x 10^9; hemoglobin ≥ 9 g/dL without transfusion within 1 week preceding study drug administration
Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present);
Renal: creatinine clearance ≥60 mL/min based either on cockroft-Gault estimate or based on urine collection (12 or 24 hour);
Metabolic: Glycosylated hemoglobin (HbA1c)<7.0%, fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL
Ability to swallow oral medications.
Must be able to fast for glucose monitoring throughout PIKTOR treatment.
Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
Brain metastases which have been treated
No evidence of disease progression for ≥2 months before the first dose of study drug.
No hemorrhage after treatment
Off-treatment with dexamethasone for 3 weeks before administration of the first dose of PIKTOR
No ongoing requirement for dexamethasone or anti-epileptic drugs
Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Who cannot join

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
Leptomeningeal disease that is symptomatic or cytology-proven.
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
Known human immunodeficiency virus infection.
Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

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Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Breast feeding or pregnant.
Treatment with any investigational products within 30 days before the first dose of study drug
Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of PIKTOR. In addition, patients with enteric stomata are also excluded.
History of any of the following within the last 6 months before administration of the first dose of the drug:
Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
Placement of a pacemaker for control of rhythm
New York Heart Association (NYHA) Class III or IV heart failure f. Pulmonary embolism
Significant active cardiovascular or pulmonary disease including:
Uncontrolled hypertension (ie, systolic blood pressure >180 mm Hg, diastolic blood pressure > 100 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is allowed.
Pulmonary hypertension
Need for supplemental oxygen
Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement
Medically significant (symptomatic) bradycardia
History of arrhythmia requiring an implantable cardiac defibrillator
Baseline prolongation of the rate-corrected QT interval (QTc) (eg, repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)
Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) > 7%; patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in this study if all other inclusion/exclusion criteria are met.
Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C19 or CYP2C19 within 1 week preceding the first dose of study drug (See Appendix IV).
Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug.
Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of study drug

Trial locations and contacts

1 site in 1 country.

United States1 site

Baylor University Medical Center
Dallas, Texas, 75246

Other trials in United States

About this study

Official title: Phase II Clinical Trial of Treatment With TAK-228 and TAK-117 to Inhibit Homologous Recombination (HR) Followed by Cisplatin and Nab Paclitaxel in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer

This study evaluates efficacy of TAK- 228 and TAK- 117 followed by cisplatin and nab paclitaxel in patients with metastatic triple negative breast cancer.

Read the detailed description

Seventy to eighty percent of breast cancers have a gene expression profile which is characterized by homologous recombination deficiency (HRD) and high proliferation. HRD leads to errors in DNA pathway [non -homologous end joining (NHEJ)] that repair DNA-breaks, a process required for metastatic triple negative breast cancer (TNBC) survival. The hypothesis of this pilot trial is that administration of the oral combination of TAK-228 and TAK-117 (PIKTOR) will inhibit NHEJ in metastatic TNBC, leading at the time of disease progression to metastases that are HR-deficient and sensitive to cisplatin plus nab paclitaxel therapy.

Conditions: Triple Negative Breast Cancer
Being tested: Tak-228 & Tak-117, Cisplatin & Nab Paclitaxel
Medical subject headings: Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tak-228 & Tak-117Drug
Patients will receive 4mg oral TAK-228 and 200mg TAK-117 tablets until disease progression.
Cisplatin & Nab PaclitaxelDrug
following Tak-228 \& Tak-117 standard nab paclitaxel 175-220 mg/m2 plus cisplatin 60-75 mg/m2 infusion for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion

Study groups in NCT03193853
Study group	Role	What they receive
Tak + cisplatin and nab paclitaxel	Experimental	Patients with metastatic TNBC who meet the enrollment criteria will receive TAK-228 and TAK-117 until disease progression followed by nab paclitaxel plus cisplatin for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion. Receives: Drug: Tak-228 & Tak-117; Drug: Cisplatin & Nab Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Efficacy (Objective Response Rate)
To assess the objective response rate associated with sequential treatment of the oral combination TAK 228 and 117 followed by nab-paclitaxel plus cisplatin in metastatic TNBC. Objective response is measured as prolonged clinical benefit; clinical benefit is defined as progression free survival on study therapy for at least 6 months.
Measured: Through study completion, up to 2 years 8 months

Secondary outcomes (3)

Efficacy (Duration of Response)
To assess duration of response associated with sequential treatment of the oral combination Tak 228 and 117 followed by nab-paclitaxel plus cisplatin. Duration of response is measured as prolonged clinical benefit; clinical benefit is defines as progression free survival on study therapy for at least 6 months.
Measured: Through study completion, up to 2 years 8 months
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0".
To assess safety associated with sequential treatment of the oral combination Tak 228 and 117 followed by nab-paclitaxel plus cisplatin
Measured: For up to 30 days following last dose, approximately 7 months
Number of Treatment-Emergent Adverse Events (Safety and Tolerability)
To assess safety associated with sequential treatment of the oral combination TAK 228 and TAK 117 followed by nab-paclitaxel plus cisplatin per CTCAE v4.0 criteria.
Measured: For up to 30 days following last dose, approximately 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jul 20171 Dec 2022

First posted21 Jun 2017
Study start18 Jul 2017
Primary completion17 Mar 2020
Study completion1 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Patients with metastatic TNBC who meet the enrollment criteria will receive TAK-228 and TAK-117 until disease progression followed by nab paclitaxel plus cisplatin.
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03193853
Sponsor's protocol ID: 017- 113
Other IDs: Baylor 017-113
Status last verified: Aug 2023
First submitted: 9 Jun 2017
Last updated: 7 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: The Investigators will share de-identified data with Takeda for information/publication purposes

Publications

Lang JD, Nguyen TVV, Levin MK, Blas PE, Williams HL, Rodriguez ESR, Briones N, Mueller C, Selleck W, Moore S, Zismann VL, Hendricks WPD, Espina V, O'Shaughnessy J. Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel. Biomark Res. 2023 Jul 25;11(1):73. doi: 10.1186/s40364-023-00511-7.
PubMed 37491309

Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Clinical Trial of Treatment With TAK-228 and TAK-117 to Inhibit Homologous Recombination (HR) Followed by Cisplatin and Nab Paclitaxel in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer
ClinicalTrials.gov ID: NCT03193853
Acronym / sponsor ID: 017- 113
Conditions: Triple Negative Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Joyce O'ShaughnessyUniversity, hospital or other
Collaborators: Takeda
Study start: 18 Jul 2017 (actual)
Primary completion: 17 Mar 2020 (actual)
Study completion: 1 Dec 2022 (actual)
First posted: 21 Jun 2017 (actual)
Results: Posted 9 May 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study evaluates efficacy of TAK- 228 and TAK- 117 followed by cisplatin and nab paclitaxel in patients with metastatic triple negative breast cancer.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Patients with metastatic TNBC who meet the enrollment criteria will receive TAK-228 and TAK-117 until disease progression followed by nab paclitaxel plus cisplatin.

Arm	Type	Receives
Tak + cisplatin and nab paclitaxel	Experimental	Drug: Tak-228 & Tak-117, Drug: Cisplatin & Nab PaclitaxelPatients with metastatic TNBC who meet the enrollment criteria will receive TAK-228 and TAK-117 until disease progression followed by nab paclitaxel plus cisplatin for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (25 listed)

Female patients 18 years or older.
Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required.
Have not received more than 3 prior chemotherapy regimens for metastatic disease. Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is permitted.
Androgen receptor-negative (less than 10% positive nuclei) on standard IHC performed at the local pathology laboratory.
Have locoregional (eg, breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy.

Key exclusion criteria (29 listed)

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
Leptomeningeal disease that is symptomatic or cytology-proven.
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
Known human immunodeficiency virus infection.
Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tak-228 & Tak-117Patients will receive 4mg oral TAK-228 and 200mg TAK-117 tablets until disease progression.	Drug	Tak + cisplatin and nab paclitaxel
Cisplatin & Nab Paclitaxelfollowing Tak-228 \& Tak-117 standard nab paclitaxel 175-220 mg/m2 plus cisplatin 60-75 mg/m2 infusion for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion	Drug	Tak + cisplatin and nab paclitaxel

Primary outcome

Efficacy (Objective Response Rate)
Time frame: Through study completion, up to 2 years 8 months
To assess the objective response rate associated with sequential treatment of the oral combination TAK 228 and 117 followed by nab-paclitaxel plus cisplatin in metastatic TNBC. Objective response is measured as prolonged clinical benefit; clinical benefit is defined as progression free survival on study therapy for at least 6 months.

3 secondary outcomes

Efficacy (Duration of Response)
Time frame: Through study completion, up to 2 years 8 months
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0".
Time frame: For up to 30 days following last dose, approximately 7 months
Number of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: For up to 30 days following last dose, approximately 7 months

Results and safety

Results posted to the registry on 9 May 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tak + Cisplatin and Nab Paclitaxel	10	4

Primary outcome: Efficacy (Objective Response Rate)

Time frame: Through study completion, up to 2 years 8 months. Count of participants. Unit: Participants

Measure	Tak + Cisplatin and Nab Paclitaxel n = 10
Value	1

Population analysed: All participants who received at least one dose of treatment.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: For up to 30 days following last dose, approximately 7 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tak + Cisplatin and Nab Paclitaxel	4 of 10 (40%)	10 of 10 (100%)	6 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37491309Lang JD, Nguyen TVV, Levin MK, Blas PE, Williams HL, Rodriguez ESR, Briones N, Mueller C, Selleck W, Moore S, Zismann VL, Hendricks WPD, Espina V, O'Shaughnessy J. Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel. Biomark Res. 2023 Jul 25;11(1):73. doi: 10.1186/s40364-023-00511-7.
Individual participant dataSharing planned: Yes. The Investigators will share de-identified data with Takeda for information/publication purposes

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Joyce O'Shaughnessy, MD principal investigator

Baylor Scott & White Research Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tak-228 & Tak-117 and Cisplatin & Nab Paclitaxel in people with Triple Negative Breast Cancer, run by Joyce O'Shaughnessy at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy (Objective Response Rate) (time frame: Through study completion, up to 2 years 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03193853, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2023.